Embodiments of the present invention provide diagnostic markers of immunosenescence and methods of identifying individuals with impaired immune function based on a combination of such markers obtained from various analyses, primarily from blood, testing immune function including the analysis of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines (‘cytokine response’). Particular combinations of markers can predict with high accuracy whether an individual will respond to active vaccination and become protected against recurring diseases.